In a phase 2 study of heavily pretreated patients with advanced anal squamous cell carcinoma (ASCC), pembrolizumab was active and yielded manageable toxicity, regardless of PD-L1 status, according to data being presented at the virtual 2020 ASCO Annual Meeting.

Limited therapies are available for the second-line or later treatment of patients with ASCC. However, pembrolizumab has shown antitumor activity in several tumor types (including ASCC) in the phase 1b KEYNOTE-028 clinical trial. 

In the open-label, multi-cohort KEYNOTE-158 study, Aurélien Marabelle MD, PhD, Gustave Roussy, Villejuif, France, and colleagues sought to verify these findings by assessing the safety and antitumor activity of pembrolizumab therapy for previously treated, advanced cancer.

Specifically, they looked at a subgroup of 112 patients (median age, 61 years) with metastatic and/or unresectable ASCC who did not respond to prior therapy or are intolerant of standard first-line therapy. These patients all had tissue samples deemed evaluable for PD-L1 and biomarker analysis.

The primary end point of the study was the objective response rate, which was evaluated every 9 weeks for 1 year, then every 12 weeks thereafter, and secondary end points included response duration, overall survival, progression-free survival, and safety.

All patients received pembrolizumab 200 mg every 3 weeks until disease progression, unacceptable toxicity, or completion of 35 cycles occurred.

Dr Marabelle et al used the PD-L1 IHC 22C3 pharmDx assay to evaluate PD-L1 expression

As of December 6, 2018 (the point of data cutoff), 10 (8.9%) patients had completed 35 cycles of treatment and 102 had discontinued therapy. The median follow-up time frame was 12 months, and the median duration of response was not reached.

The objective response rate was 11.6% (95% CI, 6.3-19.0), including 5 patients with a complete response and 8 with a partial response.

Among 75 patients with a PD-L1 combined positive score (CPS) ≥1 and 30 with PD-L1 CPS <1, a respective total of 11 (14.7%) and 2 (6.7%) patients had responses.

In addition, across all 112 patients, the median durations of overall survival and progression-free survival were 12 months (95% CI, 9.1-15.4) and 2 months (95% CI, 2.0-2.1), respectively.

68 (60.7%) patients had Treatment-related adverse events were reported in 68 (60.7%) of patients, including 21 (18.8%) with grade 3-5 events. Although there were no treatment-related deaths documented, 4 (3.6%) patients discontinued therapy because of treatment-related adverse events.

“Pembrolizumab demonstrated antitumor activity and manageable toxicity in patients with heavily pretreated advanced ASCC, regardless of PD-L1 status,” Dr Marabelle and colleagues concluded.—Hina M. Porcelli

Marabelle A, Cassier PA, Fakih M, et al. Pembrolizumab for advanced anal squamous cell carcinoma (ASCC): Results from the multicohort, phase II KEYNOTE-158 study. Presented at: the 2020 ASCO Annual Meeting; May 29-31, 2020. Abstract 1.